Effect of β-Blockers on Cardiac Function and Calcium Handling Protein in Postinfarction Heart Failure Rats

• Published in: Chest Vol. 128; no. 3; p. 1812
• Main Authors: Yi-Lan Sun, Shen-Jiang Hu, Li-Hong Wang, Ying Hu, Jian-Ying Zhou
• Format: Journal Article
• Language: English
• Published: American College of Chest Physicians 01.09.2005
• DOI: 10.1378/chest.128.3.1812
• ISSN: 0012-3692

Objectives: The normal expression of Ca 2+ -handling protein is critical for efficient myocardial function. The present study was designed to test the hypothesis that β-blocker treatment may attenuate left ventricular (LV) remodeling and cardiac contractile dysfunction in the failing heart, which may be associated with alterations of Ca 2+ -handling protein Methods: We investigated the change of LV remodeling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 mg/kg/d) or metoprolol (60 mg/kg/d) treatment for 6 weeks (n = 9 in the MI plus carvedilol group, and n = 8 in every other group). The expression of messenger RNA and proteins of sarcoplasmic reticulum Ca 2+ -adenosine triphosphatase (SERCA) and phospholamban in cardiomyocytes of all rats were also measured Results: There was significant LV remodeling and cardiac contractile dysfunction in MI rats. The messenger RNA and protein expression of SERCA were down-regulated (p < 0.01), but the expression of phospholamban messenger RNA and protein were up-regulated (p < 0.01) in MI rats compared to sham-operated rats. After the treatment with β-blockers, LV remodeling and function were clearly improved. Carvedilol was better in attenuating the weight of the LV and the relative weight of the right ventricle than metoprolol (p < 0.05). β-Blockers restored the low expression of SERCA (p < 0.05) but showed no effect on phospholamban expression (p > 0.05). Moreover, carvedilol induced a more significant improvement of SERCA expression than metoprolol (p < 0.05) Conclusions: β-Blockers are effective in preventing LV remodeling and cardiac contractile dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA expression.